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Clinical Impact of Next-Generation Sequencing-Guided Targeted Therapies in Advanced Cancer: A Systematic Review and
F Kazmi1, R Katyal1, T F D Liu1
1Department of Oncology, Norfolk and Norwich University Hospital, Norwich, NR4 7UY, UK.
Clinical Oncology (Royal College of Radiologists (Great Britain))
|October 16, 2025
Summary
Next-generation sequencing (NGS)-guided matched targeted therapies (MTTs) improve progression-free survival in advanced cancers, particularly when combined with standard of care (SOC). Overall survival benefits are tumor-specific, and increased toxicity necessitates careful patient selection.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- Precision oncology utilizes next-generation sequencing (NGS) for targeted therapies in cancer.
- The efficacy of matched targeted therapies (MTTs) in relapsed or metastatic cancer is not well-established.
- This review focuses on advanced solid and hematological tumors.
Purpose of the Study:
- To evaluate the efficacy and safety of NGS-guided MTTs in advanced cancers.
- To compare MTTs (alone or with SOC) against SOC alone.
- To analyze progression-free survival (PFS), overall survival (OS), and adverse events.
Main Methods:
- Systematic review and meta-analysis of 30 randomized controlled trials (RCTs) including 7393 patients.
- Searches included CENTRAL, MEDLINE, EMBASE, reference lists, and conference proceedings up to October 2024.
- Random-effects meta-analysis using the DerSimonian-Laird method.
Main Results:
- MTTs reduced disease progression risk by 30-40%.
- No consistent OS benefit with MTT monotherapy; combination with SOC improved OS in prostate and urothelial cancers.
- MTTs increased toxicity, especially in combination regimens; most studies had high risk of bias.
Conclusions:
- NGS-guided MTTs significantly improve PFS, especially with SOC.
- OS benefits are tumor-specific; increased toxicity requires careful patient selection.
- Routine genomic profiling is recommended for advanced or recurrent cancers.
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